They describe their model in the January 2010 issue of the Journal of Neuropathology and Experimental Neurology.
Specialized vascular system
“The barrier is known as the blood-nerve barrier and it regulates how peripheral nerves work. Peripheral nerves connect the central nervous system to the muscles of the limbs and sensory organs. This ‘gate keeper’ is a specialized vascular system that allows for proper nerve function by enabling the necessary nutrients in blood to flow in and unwanted material out,” said Dr. Eroboghene E. Ubogu, assistant professor of neurology and director of the Neuromuscular Immunopathology Research Laboratory at BCM.
Ubogu, who is the senior author on the study, added that very little is known about how the human blood-nerve barrier normally works or how it is altered when the peripheral nerves are diseased. The cells that make up the blood-nerve barrier are hard to study and extract because they are surrounded by a large amount of connective tissue, are present deep within the innermost layers and represent less than 1 percent of all cells found in peripheral nerves.
Ubogu and his research colleagues, including lead author research assistant Nejla Yosef and Dr. Robin H. Xia, a postdoctoral research associate, both in the department of neurology at BCM, began by isolating these specialized blood vessel cells from the sciatic nerve, the largest nerve in the body found at the back of the thighs.
“It started as trial and error since methods for this type of work had not been outlined for human peripheral nerves,” Ubogu said. “We looked at how other blood vessel and nerve cells were isolated from humans and other animals and modified those protocols until we achieved our goal.”
It took more than six tries of a process involving multiple steps before Ubogu and his team were successful in isolating the blood vessel cells that make up the blood-nerve barrier.
Prior to developing the blood-nerve barrier model, Ubogu and his colleagues used several laboratory methods to verify that these specialized blood vessel cells, called primary human endoneurial endothelial cells, were the cells that formed blood vessels within the innermost layer of peripheral nerves.
Better view of diseases
These cells were grown in laboratory dishes, and used to develop a blood-nerve barrier model system that behaves very similar to what is seen or expected in humans. This model will allow researchers to study how substances dissolved in the bloodstream, large molecules, drugs, microorganisms and white blood cells are able to enter or exit the peripheral nerves and why their movements may be restricted or permitted in times of health or disease.
“We can now see the gate, and if we understand how it is locked, opened and closed, we may be able to treat certain nerve diseases more effectively or even prevent them,” said Ubogu.
This model will give researchers a better view of how diseases such as HIV and diabetes affect the peripheral nervous system. Guillain-Barré syndrome and chronic demyelinating inflammatory polyneuropathy (peripheral nerve inflammation that leads to a loss of movement or sensation) are also disorders that can be further investigated because of this research. A better understanding of how drugs get into peripheral nerves is also possible with this model.
“I would like research collaborations to grow from these findings,” Ubogu said. “The hope is that labs already studying peripheral nerve function and disease will be able to use the model to further their work.”
All researchers are with the Neuromuscular Immunopathology Research Laboratory at BCM.
The study was supported Guillain-Barré Syndrome/Chronic Inflammatory Demyelinating Polyradiculoneuropathy Foundation International Research Grant and by the BCM New Investigator Start-Up Program.